Search

Background: Traffic-related air pollution especially in highly socioeconomically developed megacity is usually considered as a severe problem leading to inevitable adverse health outcomes. This study aimed to investigate the associations between traffic-related air pollutants with risk of dry eye disease (DED) outpatient visits in a megacity (Guangzhou) along the subtropical coast in South China. Methods: Daily data on DED outpatient visits and environmental variables from 1 January 2014 to 31 December 2020 in Guangzhou were obtained. A time-series study using a quasi-Poisson generalized linear model (GLM) combined with distributed lag non-linear model (DLNM) was adopted. Subgroup analyses stratified by age, gender, and season were conducted. Results: Totally, 27, 828 DED cases were identified during the study period including 2557 days. Daily number of outpatient visits for DED ranged from 0 to 41. An increase of 10 μg/m3 in PM2.5, NO2 and SO2 concentration was associated with 3.1%, 5.9% and 17.4% increase in the risk of DED outpatient visits, respectively (RRPM2.5 = 1.031, 95%CI: 1.004–1.059, lag 0–11 day; RRNO2 = 1.059, 95% CI: 1.027–1.092, lag0-14 day; RRSO2 = 1.174, 95% CI: 1.036–1.330, lag0-13 day). Subgroup analyses indicated that the effects of PM2.5 exposure on the risk of DED outpatient visits remained significant in aged < 60 years (RR max = 1.008, 95% CI: 1.003–1.013, lag0 day) and the effects of SO2 exposure on the DED outpatient visits risk remained significant in the females (RR max = 1.025, 95% CI: 1.006–1.044, lag0 day). The associations of PM2.5 (RR = 1.010, 95% CI: 1.003–1.016, lag0 day) and SO2 (RR = 1.030, 95% CI: 1.003–1.058, lag14 day) exposure with DED outpatient visits risk remained significant in warm seasons, whereas NO2 (RR = 1.006, 95% CI: 1.002–1.009, lag14 day) exposure was significantly associated with DED outpatient visits in cold seasons. The associations of PM2.5 (first visit, RR = 1.006, 95% CI: 1.001–1.011, lag0 day; re-visit, RR = 1.002, 95% CI: 1.000–1.005, lag6 day), NO2 (first visit, RR = 1.006, 95% CI: 1.001–1.012, lag0 day; re-visit, RR = 1.007, 95% CI: 1.002–1.012, lag0 day), and SO2 (first visit, RR = 1.023, 95% CI: 1.002–1.044, lag0 day; re-visit, RR = 1.023, 95% CI: 1.000–1.045, lag0 day) exposure with risk of DED outpatient visits were significant for both first- and re-visits. Conclusions: Our study revealed that short-term exposure to PM2.5, NO2 and SO2 were positively associated with risk of DED outpatient visits, especially for the youngers, females and during warm seasons, providing evidence for making public health policy to improve life quality in developed megacity. [ABSTRACT FROM AUTHOR]

Background and Aims Vascular smooth muscle cell (VSMC) phenotype switching is a pathological hallmark in various cardiovascular diseases. N4-acetylcytidine (ac4C) catalyzed by N-acetyltransferase 10 (NAT10) is well conserved in the enzymatic modification of ribonucleic acid (RNA). NAT10-mediated ac4C acetylation is involved in various physiological and pathological processes, including cardiac remodelling. However, the biological functions and underlying regulatory mechanisms of mRNA ac4C modifications in vascular diseases remain elusive. Methods By combining in-vitro and in-vivo vascular injury models, NAT10 was identified as a crucial protein involved in the promotion of post-injury neointima formation, as well as VSMC phenotype switching. The potential mechanisms of NAT10 in the vascular neointima formation were clarified by RNA sequence (RNA-seq), acetylated mRNA immunoprecipitation sequence (acRIP-seq), and RNA binding protein immunoprecipitation sequence (RIP-seq). Results NAT10 and ac4C modifications were upregulated in injured human and rodent arteries. Deletion of NAT10 in VSMCs effectively reduced post-injury neointima formation and VSMC phenotype switching. Further RNA-seq, RIP-seq, and acRIP-seq revealed that NAT10, by its ac4C modification, directly interacts with genes, including integrin-β1 (ITGB1) and collagen type I alpha 2 chain (Col1a2) mRNAs. Taking ITGB1 as one example, it showed that NAT10-mediated ac4C consequently increased ITGB1 mRNA stability and its downstream focal adhesion kinase (FAK) signaling, directly influencing the proliferation of VSMCs and vascular remodelling. The regulation of NAT10 on the VSMC phenotype is of translational significance because the administration of Remodelin, a NAT10 inhibitor, effectively prevents neointima formation by suppressing VSMC proliferation and downregulating ITGB1 expression and deactivating its FAK signaling. Conclusions This study reveals that NAT10 promotes vascular remodelling via mRNA ac4C acetylation, which may be a promising therapeutic target against vascular remodelling. [ABSTRACT FROM AUTHOR]

Background: The imbalance of glutamate (Glu) and gamma-aminobutyric acid (GABA) neurotransmitter system plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Riluzole is a Glu modulator originally approved for amyotrophic lateral sclerosis that has shown potential neuroprotective effects in various neurodegenerative disorders. However, whether riluzole can improve Glu and GABA homeostasis in AD brain and its related mechanism of action remain unknown. This study utilized chemical exchange saturation transfer (CEST) imaging combined with proton magnetic resonance spectroscopy (1H-MRS) to monitor the dynamic changes of Glu and GABA in riluzole-treated AD mice, aiming to evaluate the efficacy and mechanism of riluzole in AD treatment. Methods: GluCEST, GABACEST and 1H-MRS were used to longitudinally monitor Glu and GABA levels in 3xTg AD mice treated with riluzole (12.5 mg/kg/day) or vehicle for 20 weeks. Magnetic resonance measurements were performed at baseline, 6, 12, and 20 weeks post-treatment. Cognitive performance was assessed using the Morris Water Maze (MWM) at baseline, 10, and 20 weeks. At the study endpoint, immunohistochemistry, Nissl staining, and Western blot were used to evaluate the brain pathology, neuronal survival, and protein expression. Results: GluCEST, GABACEST and 1H-MRS consistently revealed higher levels of Glu and GABA in the brain of riluzole-treated AD mice compared to untreated controls, which were associated with improvements in spatial learning and memory. The cognitive improvements significantly correlated with the increased GluCEST signals and Glu levels. Immunohistochemistry and Nissl staining demonstrated that riluzole treatment reduced amyloid-beta (Aβ) deposition, tau hyperphosphorylation, GFAP-positive astrocyte activation, and prevented neuronal loss. Moreover, riluzole upregulated the expression of excitatory amino acid transporter 2 (EAAT2), glutamic acid decarboxylase 65/67 (GAD65/67), and glutamine synthetase (GS), suggesting enhanced neurotransmitter metabolism. Conclusions: CEST imaging combined with 1H-MRS demonstrated the effectiveness of riluzole in modulating Glu- and GABA-related changes and improving cognitive function in 3xTg AD mice, potentially through regulating key proteins involved in neurotransmitter metabolism. These findings suggest riluzole as a therapeutic agent for Alzheimer's disease and highlight the utility of multimodal MR imaging in monitoring treatment response and exploring disease mechanisms. [ABSTRACT FROM AUTHOR]

Te-free thermoelectrics have garnered significant interest due to their immense thermoelectric potential and low cost. However, most Te-free thermoelectrics have relatively low performance because of the strong electrical and thermal transport conflicts and unsatisfactory compatibility of interfaces between device materials. Here, we develop lattice defect engineering through Cu doping to realize a record-high figure of merit of ~1.9 in n-type polycrystalline PbSe. Detailed micro/nanostructural characterizations and first-principles calculations demonstrate that Cu-induced interstitial defects and nanoprecipitates simultaneously optimize electron and phonon transport properties. Moreover, a robust Co/PbSe interface is designed to effectively prevent chemical reactions/diffusion; this interface exhibited a low electrical contact resistivity of ~10.9 μΩ cm2, excellent durability, and good stability in the thermoelectric module, which achieves a record-high conversion efficiency of 13.1% at a temperature difference of 460 K in segmented thermoelectric modules. This study lays the groundwork for advancing the development of Te-free selenide-based thermoelectric materials. The authors develop lattice defect engineering through Cu doping to realize a high figure of merit in n-type polycrystalline PbSe, finding that Cu induced interstitial defects and nanoprecipitates simultaneously optimize electron and phonon transport properties. [ABSTRACT FROM AUTHOR]

AbstractObjective: This study applied a mixed-methods approach to investigate rater effects that might affect case report evaluation in China. Method: In the quantitative phase, we randomly assigned 210 mental health professionals to the experienced or novice ratee condition to rate the same structured case report on assessment and formulation, intervention strategy, relationship, and self-reflection. The qualitative phase was subsequently conducted to help make sense of the results. We interviewed twelve supervisors about how they would rate a case report and factors they thought would influence their evaluation. Results: Linear model with non-constant variances revealed that the manipulation of ratee experience did not significantly bias ratings. Raters whose self-identified theoretical orientation aligned with that of the report provided higher and less dispersed ratings for intervention strategy and therapeutic relationship competencies. As their years of experience increased, theoretically congruent raters tended to give lower and more dispersed ratings. Thematic analysis revealed highly variable cognitive processes, and identified rater theoretical expertise, evaluation context, rater subjectivity and dual relationships as important factors to consider. Conclusion: This study indicate that theoretically congruent raters would be desirable, but raters with more years of experience should be cautioned against giving stringent ratings for theoretically familiar cases. [ABSTRACT FROM AUTHOR]

Background: Uterine clear cell carcinoma (UCCC) is a rare and aggressive subtype of endometrial cancer, often presenting at an advanced stage with poor prognosis. Treatment options for advanced or recurrent UCCC are currently limited, especially after platinum-based chemotherapy has failed. Case presentation: We present the case of a 49-year-old female diagnosed with stage IV uterine clear cell carcinoma. The patient had a history of atrial fibrillation and initially received several surgical interventions and platinum-based chemotherapy, but these treatments resulted in poor outcomes and rapid tumor progression. Genetic testing showed a high tumor mutation burden (TMB-H, 42.24 mutations/Mb) with stable microsatellites and a suspected harmful mutation in the PMS2 gene. After conventional therapies failed, the patient received a combination treatment of cadonilimab (375 mg) and albumin-bound paclitaxel (380 mg) for six cycles. This was followed by cadonilimab monotherapy for maintenance. This treatment regimen led to a complete response (CR), with no detectable abdominal fluid or enlarged lymph nodes by January 4, 2023. The CR status was maintained during a follow-up on April 07, 2024. The adverse effects included severe myelosuppression, mild skin reactions, hypothyroidism, and Grade 3 hyperglycemia, all of which were managed symptomatically. Conclusion: This case illustrates how effective AK104/Cadonilimab (a PD-1/CTLA-4 bispecific) can be when combined with albumin-bound paclitaxel for treating advanced UCCC, especially in patients who have not responded to standard therapies. The patient's complete and lasting response shows the potential of PD-1/CTLA-4 bispecific immunotherapy. This suggests that cadonilimab could provide important clinical benefits for patients with advanced or recurrent UCCC. [ABSTRACT FROM AUTHOR]

Two‐dimensional conjugated metal–organic frameworks (2D c‐MOFs) have shown great promise in various electrochemical applications due to their intrinsic electrical conductivity. A large pore aperture is a favorable feature of this type of material because it facilitates the mass transport of chemical species and electrolytes. In this work, we propose a ligand insertion strategy in which a linear ligand is inserted into the linkage between multitopic ligands, extending the metal ion into a linear unit of ‐M‐ligand‐M‐, for the construction of 2D c‐MOFs with large pore apertures, utilizing only small ligands. As a proof‐of‐concept trial of this strategy, a 2D c‐MOF with mesopores of 3.2 nm was synthesized using commercially available ligands hexahydrotriphenylene and 2,5‐dihydroxybenzoquinone. The facilitation of the diffusion of redox species by the large pore size of this MOF was demonstrated through a series of probes. With this feature, it showed superior performance in the electrochemical analysis of a variety of biological species. [ABSTRACT FROM AUTHOR]

Anatomy forms the foundation for the training and execution of routine surgical procedures. However, a gap persists in effectively bridging anatomical knowledge with the confident performance of procedures. Virtual simulation (VS) techniques, based on experiential and situated learning theory, hold promise in addressing this challenge. Apicoectomy, a procedure involving root apex resection to preserve a tooth, requires a blend of regional and dental anatomy knowledge, making it an ideal model for assessing the effectiveness of VS. This prospective cohort study evaluated primarily the enhancement of incorporating VS training in the preclinical skill training of apicoectomy for undergraduate dental students, compared to relying solely on traditional methods. VS training includes the simulated dissection process, patient examination, and apicoectomy based on graphically synthesized virtual models. Secondly, the study investigated the influence of exposure to VS training on students' confidence and satisfaction. The training was divided into three progressive levels aligned with students' cognitive processes, employing Miller's competence learning framework. Participants were categorized into the control group (CG) (n = 214) and VS training group (VSTG) (n = 220) based on their classes. The results demonstrated that VSTG showed significantly greater training enhancement (VSTG: 7.14 ± 1.74; CG: 6.57 ± 2.02, p = 0.002) and higher confidence levels (VSTG: 2.94 ± 0.13; CG: 2.69 ± 0.13, p < 0.001), along with greater satisfaction with the training compared to the CG (VSTG: 3.70 ± 0.18; CG: 3.20 ± 0.17, p < 0.001). In conclusion, VS proves to be a valuable adjunct for enhancing procedural skill training in surgical procedures. [ABSTRACT FROM AUTHOR]

Aims: Few personalized monitoring models for valproic acid (VPA) in pediatric epilepsy patients (PEPs) incorporate machine learning (ML) algorithms. This study aimed to develop an ensemble ML model for VPA monitoring to enhance clinical precision of VPA usage. Methods: A dataset comprising 366 VPA trough concentrations from 252 PEPs, along with 19 covariates and the target variable (VPA trough concentration), was refined by Spearman correlation and multicollinearity testing (366 × 11). The dataset was split into a training set (292) and testing set (74) at a ratio of 8:2. An ensemble model was formulated by Gradient Boosting Regression Trees (GBRT), Random Forest Regression (RFR), and Support Vector Regression (SVR), and assessed by SHapley Additive exPlanations (SHAP) analysis for covariate importance. The model was optimized for R2, relative accuracy, and absolute accuracy, and validated against two independent external datasets (32 in-hospital and 28 out-of-hospital dataset). Results: Using the R2 weight ratio of GBRT, RFR and SVR optimized at 5:2:3, the ensemble model demonstrated superior performance in terms of relative accuracy (87.8%), absolute accuracy (78.4%), and R2 (0.50), while also exhibiting a lower Mean Absolute Error (9.87) and Root Mean Squared Error (12.24), as validated by the external datasets. Platelet count (PLT) and VPA daily dose were identified as pivotal covariates. Conclusion: The proposed ensemble model effectively monitors VPA trough concentrations in PEPs. By integrating covariates across various ML algorithms, it delivers results closely aligned with clinical practice, offering substantial clinical value for the guided use of VPA. [ABSTRACT FROM AUTHOR]

Factor Ⅺ (FⅪ) plays a major role in thrombus amplification and an ancillary role in hemostasis. This differential contribution is expected to provide new ideas for the prevention and treatment of thrombotic diseases by targeting FⅪ as a potentially safer anticoagulation strategy. Currently, an increasing number of FⅪ inhibitors are entering phaseⅢ clinical trials, and although these inhibitors showed promising clinical potential, the strategies for monitoring and reversing the effects of these inhibitors remain unclear, which poses new challenges for laboratory monitoring and clinical practice. This review, based on the physiological function of FⅪ and FⅪ inhibitors under study, systematically explored the laboratory evidence of coagulation activity linked to these inhibitors, summarized potential methods of reversal in combination with the treatment protocols of inherited FⅪ deficiency, which provided certain references for the development of clinical treatment protocols and reversal strategies.